Vascular restenosis is a major long-term complication following surgical intervention of blocked arteries by percutaneous transluminal coronary angioplasty (PTCA), atherectomy, laser angioplasty and arterial bypass graft surgery. In about 35% of the patients who undergo PTCA, reocclusion occurs within three to six months after the procedure. The current strategies for treating vascular restenosis include mechanical intervention by devices such as stents or pharmacologic therapies including heparin, low molecular weight heparin, coumarin, aspirin, fish oil, calcium antagonist, steroids, and prostacyclin.
In the pathogenesis of restenosis excessive cell proliferation and migration occurs as a result of growth factors produced by cellular constituents in the blood and the damaged arterial vessel wall that mediate the proliferation of smooth muscle cells in vascular restenosis. Agents that inhibit the proliferation and/or migration of smooth muscle are useful in the treatment and prevention of restenosis. Further, agents that inhibit the inflammatory response of smooth muscle are useful in the treatment and prevention of restenosis. The present invention provides for the use of wortmannin and certain analogs as restenosis inhibitors.
The invention provides wortmannin analogs useful in the inhibition of restenosis in a subject. The invention is comprised of stents or other devices such as bioprosthetic implants that may be coated with the wortmannin analogs. The present invention is also directed to methods comprised of administering wortmannin analogs to a subject at a pharmaceutically effective dose of a compound. The wortmannin analogs may be any of those described herein, but are preferably selected from the group of consisting of those wortmannin analogs described in FIGS. 1-3, even more preferably FIG. 2. The wortmannin analogs of the present invention expected to be useful in treating restenosis are represented by the following general chemical formula: 
Wherein Y is a heteroatom, preferably N or S, and R1 or R2 are unsaturated alkyl, non-linear alky, branched alky, substituted alkyl or cyclic alkyl.